Enalapril



Better Known as: Vasotec

 * Marketed By: Merck & Co.


 * Major Indication: Hypertension & Congestive Heart Failure


 * Drug Class: ACE Inhibitor
 * Date of FDA Approval (Patent Expiration): 1985 (2000)


 * 1996 Peak Sales: $2.5 Billion
 * Importance: One of the best selling Angiotensin-Converting Enzyme Inhibitors of all time. Was developed by Merck as a replacement for Captopril with a better side effect profile.
 * See Pharmaceutical Drugs for more information about other drugs and diseases.

Mechanism of Action
Angiotensin II has been implicated in cardiac, renal and vascular diseases. Bradykinin, a small peptide that counterbalance the effects of Angiotensin II by acting as a strong vasodilator upon binding AT2, is degraded by the same ACE-1 enzyme. Since ACE-1 is the primary producer of Angiotensin II and degrader of Bradykinins, inhibition of ACE-1 has proven an effective treatment for Hypertension and Congestive Heart Failure. Enalapril is quickly metabolized into Enalaprilat, the more active metabolite of Enalapril predominantly by the Hepatic enzyme CYP3A4. Enalaprilat binds to the active site of Angiotensin-Converting Enzyme, preventing ACE-1 from binding and converting Angiotensin I into Angiotensin II. Enalaprilat is bound to ACE-1 via electrostatic interactions with His 353, Ala 354 (Backbone oxygen), Glue 384, Lys 511, His 513, Tyr 520 and Tyr 523 along with the zinc cation.